High MACC1 expression in combination with mutated KRAS G13 indicates poor survival of colorectal cancer patients

Molecular Cancer

Short Communication

Peter M Schlag¹  Susen Burock¹  Katharina Ilm²  Marc Osterland²  Wolfgang Kemmner²  Pia Herrmann²  Gudrun Koch²  Ulrike Stein³ 

[1] Charité Comprehensive Cancer Center, Berlin, Germany;Experimental and Clinical Research Center, Charité University Medicine Berlin and Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Str.10, 13125, Berlin, Germany;Experimental and Clinical Research Center, Charité University Medicine Berlin and Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Str.10, 13125, Berlin, Germany;German Cancer Consortium, Heidelberg, Germany;

关键词: KRAS mutations;    MACC1;    Prognostic marker;    Colorectal cancer;    Metastasis-free survival;   

DOI  :  10.1186/s12943-015-0316-2

 received in 2014-09-12, accepted in 2015-02-05,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundThe metastasis-associated in colon cancer 1 (MACC1) gene has been identified as prognostic biomarker for colorectal cancer (CRC). Here, we aimed at the refinement of risk assessment by separate and combined survival analyses of MACC1 expression with any of the markers KRAS mutated in codon 12 (KRAS G12) or codon 13 (KRAS G13), BRAF V600 mutation and MSI status in a retrospective study of 99 CRC patients with tumors UICC staged I, II and III.FindingsWe showed that only high MACC1 expression (HR: 6.09, 95% CI: 2.50-14.85, P < 0.001) and KRAS G13 mutation (HR: 5.19, 95% CI: 1.06-25.45, P = 0.042) were independent prognostic markers for shorter metastasis-free survival (MFS). Accordingly, Cox regression analysis revealed that patients with high MACC1 expression and KRAS G13 mutation exhibited the worst prognosis (HR: 14.48, 95% CI: 3.37-62.18, P < 0.001). Patients were classified based on their molecular characteristics into four clusters with significant differences in MFS (P = 0.003) by using the SPSS 2-step cluster function and Kaplan-Meier survival analysis.ConclusionAccording to our results, patients with high MACC1 expression and mutated KRAS G13 exhibited the highest risk for metachronous metastases formation. Moreover, we demonstrated that the “Traditional pathway” with an intermediate risk for metastasis formation can be further subdivided by assessing MACC1 expression into a low and high risk group with regard to MFS prognosis. This is the first report showing that identification of CRC patients at high risk for metastasis is possible by assessing MACC1 expression in combination with KRAS G13 mutation.

【 授权许可】

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© Ilm et al.; licensee BioMed Central. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.